UA team using moth protein to seek disease cures

[Source: ALAN FISCHER, Tucson Citizen] - A protein the hawk moth uses to detect odors is leading University of Arizona researchers toward possible therapies for high blood pressure, wound healing, cancer and other human maladies.

Nitric oxide, or NO, a gas produced in all human cells, is involved in many processes that determine how our bodies work, said William R. Montfort, UA professor of biochemistry and molecular biophysics and chemistry.

A protein called soluble guanylyl cyclase, or sGC, interacts with NO to affect areas of physiology including blood pressure, brain memory formation, blood coagulation and cancer metastasis, Montfort said.
With a better understanding of how sGC interacts with NO, researchers are working to develop drugs to resolve such health problems, he said.

"The right compound is a billion dollar compound," he said. "It could help millions of people."
"We have compounds that may lead to drugs and we will be pursuing them with a vengeance," he said. "The regulation of the protein - how you turn it on and turn it off - will be the key.

"We are gearing up to do straight forward drug discovery," he said. "A really useful compound would be one that stimulates sGC and lowers blood pressure or interferes with the metastasis in cancer."

Montfort's team began working with human sGC, but technical problems made research progress slow, he said.

At about the same time, Alan Nighorn, a UA neurobiology professor, was studying how hawk moths recognize odors using a process that includes their sGC.

Hawk moth sGC proved more robust and better for Montfort's research.

The team's research, published in the Journal of Biological Chemistry, is funded with National Institutes of Health grants totaling $2.5 million, he said.

Montfort, who is affiliated with the UA's BIO5 Institute, Arizona Cancer Center and Sarver Heart Center, said the project has broadly involved the UA science community.

"We've covered the entire university with this project. The key is to think broadly," he said.

The team's work, which was anchored by key discoveries by UA biochemistry graduate student Xiaohui Hu, will take time to put new medicines on the shelf, Montfort said.

"We're in the early stages. It isn't going to happen overnight," he said. "We don't know when we will discover a compound that will translate into the clinic that will relieve blood pressure or overcome the metastasis of cancer."

The primary target now is cardiovascular, finding ways to alleviate high blood pressure problems, he said.
Wound healing, asthma and cancer are others that will be pursued, he said.

In addition to trying to resolve human health problems, the team is pushed by the process of discovery, Montfort said.

"The beauty of the science is also a part of the story," he said.